{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:07:21Z","timestamp":1792260441956,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U19-NS110456"],"award-info":[{"award-number":["U19-NS110456"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Synucleinopathies are neurodegenerative disorders defined by the pathological aggregation of \u03b1-synuclein. Several \u03b1-synuclein biomarkers have been developed to aid diagnosis and research, such as cerebrospinal fluid (CSF) and blood-based measurements, seed amplification assays (SAAs), and immunohistochemical detection from skin biopsies. While these existing biomarkers have important uses, they face limitations in diagnostic specificity, spatial localization, and the ability to monitor disease progression or response to therapy. The development of \u03b1-synuclein PET tracers, which would allow for the direct in vivo imaging of \u03b1-synuclein, represents an important unmet need in both research and the clinical care of patients with movement disorders. This review outlines the current landscape of \u03b1-synuclein biomarkers and discusses both the scientific and technical challenges in developing \u03b1-synuclein PET imaging tracers.<\/jats:p>","DOI":"10.3390\/cells14161272","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:31:37Z","timestamp":1755516697000},"page":"1272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Current Status of \u03b1-Synuclein Biomarkers and the Need for \u03b1-Synuclein PET Tracers"],"prefix":"10.3390","volume":"14","author":[{"given":"Sara E.","family":"Berman","sequence":"first","affiliation":[{"name":"Parkinson\u2019s Disease and Movement Disorders Center, Department of Neurology, Pennsylvania Hospital, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease and Movement Disorders Center, Department of Neurology, Pennsylvania Hospital, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.tins.2022.11.007","article-title":"\u03b1-Synuclein in synaptic function and dysfunction","volume":"46","author":"Sharma","year":"2022","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0304-3940(98)00407-8","article-title":"\u03b1-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy","volume":"249","author":"Wakabayashi","year":"1998","journal-title":"Neurosci. 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